Revision Bulletin
Official March 1, 2010
Diclofenac Sodium Extended-Release
Tablets
Diclofenac Sodium Extended-Release Tablets contain
not less than 90.0 percent and not more than 110.0 per-
cent of the labeled amount of diclofenac sodium
(C14H10Cl2NNaO2).
Packaging and storagePreserve in well-closed containers. Store
at controlled room temperature, and protect from light.
LabelingWhen more than one Dissolution Test is given, the la-
beling states the Dissolution Test used only if Test 1 is not used.
USP Reference standards 11USP Diclofenac Sodium RS. USP
Diclofenac Related Compound A RS.
Identification
A: The retention time of the major peak in the chromatogram
of the Assay preparation corresponds to that in the chromatogram
of the Standard preparation, as obtained in the Assay.
B: Thin-Layer Chromatographic Identification Test 201
Solvent system: methanol, toluene, glacial acetic acid
(40 : 60 : 0.5).
Test solutionFinely powder not fewer than 10 Tablets. Accu-
rately weigh a portion of the powder, equivalent to about 50 mg of
diclofenac sodium, and transfer to a 25-mL volumetric flask. Add
about 15 mL of methanol, sonicate for 10 minutes, shake by me-
chanical means for 10 minutes, dilute with methanol to volume, and
mix. Centrifuge this solution, and use the clear supernatant as the
Test solution.
Standard solutionAccurately weigh about 50 mg of USP
Diclofenac Sodium RS into a 25-mL volumetric flask. Add 10 mL
of methanol, shake by mechanical means for 10 minutes, dilute with
methanol to volume, and mix.
Change to read:
Dissolution 711
TEST 1
Medium: 0.05 M phosphate buffer, pH 7.5; 900 mL.
Apparatus 2: 50 rpm; use wire sinkers.
Times: 1, 5, 10, 16, and 24 hours.
ProcedureDetermine the amount of C14H10Cl2NNaO2 dissolved
by employing UV absorption at the wavelength of maximum ab-
sorbance at about 276 nm on filtered portions of the solution under
test, suitably diluted with Medium, if necessary, in comparison with
a Standard solution having a known concentration of USP
Diclofenac Sodium RS in the same Medium.
TolerancesThe percentages of the labeled amount of
C14H10Cl2NNaO2 dissolved at the times specified conform to Accep-
tance Table 2.
Time (hours) Amount dissolved
1 between 15% and 35%
5 between 45% and 65%
10 between 65% and 85%
16 between 75% and 95%
24 not less than 80%
TEST 2If the product complies with this test, the labeling indi-
cates that it meets USP Dissolution Test 2.
2009 The United States Pharmacopeial Convention
Diclofenac 1
Medium, Apparatus, and ProcedureProceed as directed for
Test 1.
Times: 1, 2, 4, 6, and 10 hours.
TolerancesThe percentages of the labeled amount of
C14H10Cl2NNaO2 dissolved at the times specified conform to Accep-
tance Table 2.
Time (hours) Amount dissolved
1 not more than 28%
2 between 20% and 40%
4 between 35% and 60%
6 between 50% and 80%
10 not less than 65%
TEST 3If the product complies with this test, the labeling indi-
cates that it meets USP Dissolution Test 3.
Medium and ProcedureProceed as directed for Test 1.
Apparatus 1: 100 rpm.
Times: 2, 4, 8, and 16 hours.
TolerancesThe percentages of the labeled amount of
C14H10Cl2NNaO2 dissolved at the times specified conform to Accep-
tance Table 2.
Time (hours) Amount dissolved
2 between 22% and 42%
4 between 34% and 61%
8 between 52% and 82%
16 not less than 73%
TEST 4If the product complies with this test, the labeling indi-
cates that it meets USP Dissolution Test 4.
Medium and Procedure Proceed as directed for Test 1.
Apparatus 1: 100 rpm.
Times: 2, 4, 8, and 16 hours.
TolerancesThe percentages of the labeled amount of
C14H10Cl2NNaO2 dissolved at the times specified conform to Accep-
tance Table 2.
Time (hours) Amount dissolved
2 between 20% and 40%
4 between 35% and 55%
8 between 60% and 85%
16 not less than 85% (RB 1-Mar-2010)
(RB 1-Mar-2009)
Uniformity of dosage units 905: meet the requirements.
Assay[NOTEProtect the Assay preparation, Standard prepara-
tion, and System suitability solution from light.]
Diluent: a mixture of acetonitrile and water (43 : 57).
0.05 M Monobasic potassium phosphate bufferDissolve 6.8 g
of monobasic potassium phosphate in 950 mL of water, adjust with
dilute phosphoric acid or dilute potassium hydroxide solution to a
pH of 4.0 0.05, dilute with water to 1 L, and mix.
Mobile phasePrepare a filtered and degassed mixture of
acetonitrile, 0.05 M Monobasic potassium phosphate buffer, and
tetrahydrofuran (43 : 57 : 2). Make adjustments if necessary (see
System Suitability under Chromatography 621).
Diclofenac related compound A solutionDissolve an accurately
weighed quantity of USP Diclofenac Related Compound A RS in
Diluent, and quantitatively dilute with Diluent to obtain a solution
having a known concentration of about 200 g per mL.
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2 Diclofenac
Standard preparationDissolve an accurately weighed quantity
of USP Diclofenac Sodium RS in Diluent, and quantitatively dilute
with Diluent to obtain a solution having a known concentration of
about 200 g per mL.
System suitability solutionTransfer 10 mL of the Standard
preparation and 5 mL of Diclofenac related compound A solution
to a 20-mL volumetric flask. Dilute with Diluent to volume, and
mix.
Assay preparationPowder not fewer than 20 Tablets, and trans-
fer an accurately weighed portion of the powder, equivalent to
about 100 mg of diclofenac sodium, to a 100-mL volumetric flask,
add about 50 mL of Diluent, sonicate for about 15 minutes, then
shake by mechanical means for 15 minutes. Add a few drops of
methanol to remove the foam, dilute with Diluent to volume, and
mix. Transfer 10.0 mL of the supernatant to a 50-mL volumetric
flask, dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621)The liq-
uid chromatograph is equipped with a 254-nm detector and a 4.6-
mm 15-cm column that contains 5-m packing L1. The flow rate
is about 1.5 mL per minute. Inject 40 L of the System suitability
solution into the chromatograph, and record the peak responses as
2009 The United States Pharmacopeial Convention
Revision Bulletin
Official March 1, 2010
directed for Procedure: the relative retention times are about 0.9 for
diclofenac related compound A and 1.0 for diclofenac; and the reso-
lution, R, between the diclofenac peak and the diclofenac related
compound A peak is not less than 2.0. Inject 20 L of the Standard
preparation into the chromatograph, and record the peak responses
as directed for Procedure: the tailing factor of the diclofenac peak
is not more than 2.0; and the relative standard deviation of the
diclofenac peak for replicate injections is not more than 2.0%.
ProcedureSeparately inject equal volumes (about 20 L) of the
Standard preparation and the Assay preparation into the chromato-
graph, record the chromatograms, and measure the area responses
for the major peaks. Calculate the quantity, in mg, of diclofenac
sodium (C14H10Cl2NNaO2) in the portion of Tablets taken by the
formula:
500C(rU / rS)
in which C is the concentration, in mg per mL, of USP Diclofenac
Sodium RS in the Standard preparation; and rU and rS are the
diclofenac peak responses obtained from the Assay preparation and
the Standard preparation, respectively.
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